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Although virulence factors and antifungal resistance have been individually linked to disease severity, their integrated contribution to distinct clinical outcomes remains poorly defined. Here, we performed a comprehensive phenotypic characterization of 58 clinical C. albicans isolates recovered from women with AVVC (n\u00a0=\u00a025) or RVVC (n\u00a0=\u00a033), and C. albicans SC5314 was included for comparison. We assessed fungal dimorphism, cell surface hydrophobicity, biofilm-forming capacity (BFC), and the production of secreted aspartyl proteinases (SAP) and lipases (LIP). Antifungal susceptibility to azoles and other clinically relevant agents was determined using an automated system. Multivariate unsupervised analyses were applied to identify integrated virulence phenotypes. All clinical isolates exhibited efficient filamentation. AVVC isolates displayed enhanced adherence, biofilm metabolic activity, and LIP production, whereas RVVC isolates exhibited increased SAP activity and reduced BFC. Unsupervised clustering and UMAP analysis identified four virulence clusters, including profiles specifically associated with AVVC or RVVC, as well as mixed phenotypes. Notably, a high prevalence of azole resistance was observed in both groups, with resistance patterns aligning with specific virulence clusters. Collectively, these findings indicate that AVVC and RVVC are associated with distinct, niche-adapted C. albicans virulence programs that integrate enzymatic activity, biofilm traits, and antifungal resistance. This structured phenotypic heterogeneity provides a framework to reinterpret vulvovaginal candidiasis as a multifactorial and adaptive process with important implications for disease persistence and therapeutic failure.<\/jats:p>","DOI":"10.1093\/mmy\/myag028","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T11:28:28Z","timestamp":1775561308000},"source":"Crossref","is-referenced-by-count":1,"title":["Distinct virulence and azole resistance profiles of\n                    <i>Candida albicans<\/i>\n                    clinical isolates from patients with acute and recurrent vulvovaginal candidiasis"],"prefix":"10.1093","volume":"64","author":[{"given":"Sof\u00eda C","family":"Angiolini","sequence":"first","affiliation":[{"name":"Laboratory of Innate Immunity to Fungal Pathogens, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of C\u00f3rdoba , C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Center for Research in Clinical Biochemistry and Immunology , CIBICI-CONICET, C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Research Group of Immunology and Mycology , C\u00f3rdoba 5000 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilse","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity to Fungal Pathogens, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of C\u00f3rdoba , C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Center for Research in Clinical Biochemistry and Immunology , CIBICI-CONICET, C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Research Group of Immunology and Mycology , C\u00f3rdoba 5000 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisa","family":"Manzone-Rodriguez","sequence":"additional","affiliation":[{"name":"Center for Research in Clinical Biochemistry and Immunology , CIBICI-CONICET, C\u00f3rdoba 5000 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula A","family":"Icely","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity to Fungal Pathogens, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of C\u00f3rdoba , C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Center for Research in Clinical Biochemistry and Immunology , CIBICI-CONICET, C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Research Group of Immunology and Mycology , C\u00f3rdoba 5000 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Soledad","family":"Mir\u00f3","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity to Fungal Pathogens, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of C\u00f3rdoba , C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Center for Research in Clinical Biochemistry and Immunology , CIBICI-CONICET, C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Research Group of Immunology and Mycology , C\u00f3rdoba 5000 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio D","family":"Abiega","sequence":"additional","affiliation":[{"name":"Research Group of Immunology and Mycology , C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Laboratory of Infectious Diseases, Hospital Privado , C\u00f3rdoba 5000 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando O","family":"Riera","sequence":"additional","affiliation":[{"name":"Research Group of Immunology and Mycology , C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Division of Infectious Diseases , Sanatorio Allende, C\u00f3rdoba 5000 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Iribarren","sequence":"additional","affiliation":[{"name":"Center for Research in Clinical Biochemistry and Immunology , CIBICI-CONICET, C\u00f3rdoba 5000 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Caeiro","sequence":"additional","affiliation":[{"name":"Research Group of Immunology and Mycology , C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Division of Infectious Diseases , AltaMed Health Service Corporation, Los Angeles, 90022 California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2449-0852","authenticated-orcid":false,"given":"Claudia E","family":"Sotomayor","sequence":"additional","affiliation":[{"name":"Laboratory of Innate Immunity to Fungal Pathogens, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of C\u00f3rdoba , C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Center for Research in Clinical Biochemistry and Immunology , CIBICI-CONICET, C\u00f3rdoba 5000 ,","place":["Argentina"]},{"name":"Research Group of Immunology and Mycology , C\u00f3rdoba 5000 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"2026043011360546400_bib1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2006.00450.x","article-title":"History and update on host defense against vaginal candidiasis","volume":"6","author":"Fidel","year":"2006","journal-title":"Am J Reprod Immunol."},{"issue":"9577","key":"2026043011360546400_bib2","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1016\/S0140-6736(07)60917-9","article-title":"Vulvovaginal 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